Fig. 3

Phenotypes of both Adamts16+/- and Adamts16+/H355Q mice showing the occurrence of BAV and progressive aortic valve disease. A, Anatomic analysis of aortic valves in Adamts16+/+, Adamts16+/-, and Adamts16-/- mice. The black arrow indicates commissures. Scale bars=1 mm. B, Percentage of bicuspid aortic valve occurrence in Adamts16+/+, Adamts16+/-, and Adamts16-/- mice. P values were calculated using the Fisher exact test . C, Anatomic analysis of aortic valves in Adamts16+/+, Adamts16+/H355Q, and Adamts16H355Q/H355Q mice. The black arrow indicates commissures. Scale bars=1 mm. D, Percentage of bicuspid aortic valve occurrence in Adamts16+/+, Adamts16+/H355Q, and Adamts16H355Q/H355Q mice. P values were calculated using the Fisher exact test. All mice used for aortic valve anatomic analysis were at 3 to 12 months. E, Representative hematoxylin and eosin?stained aortic valve images in mouse transverse sections at 12 months of age. The blue dashed lines represent regions of quantification for thickness. Scale bars=200 µm. F, Quantification of aortic valve thickness reveals significant enlargement of the aortic valve leaflet hinges in Adamts16+/+, Adamts16+/-, and Adamts16+/H355Q mice (n=5 mice for each genotype; each mouse has 6 valve hinge measurements). ****P<0.0001, mean±SEM, using 1-way ANOVA followed by the Tukey post hoc test. G, Quantification of aortic valve peak velocities. Aortic valve peak velocities were significantly increased at 9 and 12 months in Adamts16+/- and Adamts16+/H355Q mice, whereas no increase was observed in Adamts16+/+ control littermates (n=8 mice for each genotype at each stage, mean±SEM, using mixed-effects ANOVA followed by the Tukey post hoc test). H, Quantification of aortic root diameter. Aortic root diameter progressively increased in 9- and 12-month-old Adamts16+/- mice, whereas no obvious increase was observed in Adamts16+/H355Q mice and Adamts16+/+ control littermates (n=8 mice for each genotype at each stage, mean±SEM, using mixed-effects ANOVA followed by the Tukey post hoc test). ****P<0.0001; ***P<0.001; **P<0.01; *P<0.05. ADAMTS indicates a disintegrin and metalloproteinase with thrombospondin motifs; Ao root, aortic root; AoV, aortic valve; and BAV, bicuspid aortic valve.